Acetonitrile → Dasatinib monohydrate

HRID 2283518Notes

Reaction equation

HRID 2283518 reaction equation
C(#N)C.Cl[C:5]1[N:10]=[C:9]([CH3:11])[N:8]=[C:7]([NH:12][C:13]2[S:14][C:15]([C:18]([NH:20][C:21]3[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][C:22]=3[Cl:28])=[O:19])=[CH:16][N:17]=2)[CH:6]=1.[OH:29][CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.C(N(CC)CC)C>CCCC[N+](CCCC)(CCCC)CCCC.[Br-].O>[CH3:27][C:26]1[CH:25]=[CH:24][CH:23]=[C:22]([Cl:28])[C:21]=1[NH:20][C:18]([C:15]1[S:14][C:13]([NH:12][C:7]2[CH:6]=[C:5]([N:35]3[CH2:36][CH2:37][N:32]([CH2:31][CH2:30][OH:29])[CH2:33][CH2:34]3)[N:10]=[C:9]([CH3:11])[N:8]=2)=[N:17][CH:16]=1)=[O:19].[OH2:19]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 76771-(2-Hydroxyethyl)piperazine2×HCID 8471TriethylamineHCID 112694102-[(6-chloro-2-methylpyrimidin-4-yl)amino]-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide

Product 1

HCID 11540687Dasatinib monohydrateYield 194.8%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolvent

Conditions

Temperature
32.5 °C

Procedure

200 ml of acetonitrile was taken in RB flask and 10.0 g of 2-((6-chloro-2-methylpyrimidin-4-yl)amino)-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide (Formula I), 19.8 g of 1-(2-Hydroxyethyl)piperazine (Formula II), 12.85 g of triethyl amine and 10.0 g of TBAB were charged into it. The reaction mass was stirred for 10-15 mins at 30-35° C. and then heated to 80° C. and stirred for 20-22 h. The completion of reaction was checked with Thin Layer Chromatography (TLC) and 300 mL of water was slowly charged. The reaction mass was stirred for 45 mins at 80° C. and then cooled to 30-35° C. and further stirred for ˜1.5 hrs. The reaction mass was filtered, washed with 20 mL water and suck dried for 10-15 min at RT. The wet compound was unloaded and air dried for 30 mins at 30-35° C. The material was loaded to a vacuum tray drier at 30-35° C. and vacuum was applied. The material was dried at 30-35° C. for 1 h and slowly dryer temperature was raised to 50-55° C. where drying was carried out for 8-10 hrs. The solid product obtained was then cooled to 30-35° C. and vacuum was released to obtain 12.5 g of the title compound.

Workup

  1. additionwere charged into it
  2. temperatureheated to 80° C.
  3. stirringstirred for 20-22 h
  4. customThe completion of reaction
  5. additionwas slowly charged
  6. stirringThe reaction mass was stirred for 45 mins at 80° C.
  7. temperaturecooled to 30-35° C.
  8. stirringfurther stirred for ˜1.5 hrs
  9. filtrationThe reaction mass was filtered
  10. washwashed with 20 mL water and suck
  11. customdried for 10-15 min at RT
  12. customair dried for 30 mins at 30-35° C
  13. customwas loaded to a vacuum tray drier at 30-35° C.
  14. customThe material was dried at 30-35° C. for 1 h
  15. temperatureslowly dryer temperature was raised to 50-55° C. where
  16. customdrying
  17. waitwas carried out for 8-10 hrs
  18. customThe solid product obtained
  19. temperaturewas then cooled to 30-35° C.

Sources & evidence

ORD record
ord-9751c7e41ccd45778de482e523404e7a
Source dataset
uspto-grants-2015_09
Patent number
US09145406B2

Reaction notes

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